{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T20:27:23Z","timestamp":1782332843098,"version":"3.54.5"},"reference-count":56,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T00:00:00Z","timestamp":1612224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2021,2,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Understanding metabolic mechanisms associated with cognitive changes preceding an Alzheimer\u2019s disease (AD) diagnosis could advance our understanding of AD progression and inform preventive methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>We investigated the metabolomics of the early changes in executive function and delayed recall, the earliest aspects of cognitive function to change in the course of AD development, in order to better understand mechanisms that could contribute to early stages and progression of this disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>This investigation used longitudinal plasma samples from the Wisconsin Registry for Alzheimer\u2019s Prevention (WRAP), a cohort of participants who were dementia free at enrollment and enriched with a parental history of AD. Metabolomic profiles were quantified for 2,324 fasting plasma samples among 1,200 participants, each with up to three study visits, which occurred every two years. Metabolites were individually tested for association with executive function and delayed recall trajectories across age.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Of 1,097 metabolites tested, levels of seven were associated with executive function trajectories, including an amino acid cysteine S-sulfate and three fatty acids, including erucate (22\u200a:\u200a1n9), while none were associated with delayed recall trajectories. Replication was attempted for four of these metabolites that were present in the Vietnam Era Twin Study of Aging (VETSA). Although none reached statistical significance, three of these associations showed consistent effectdirections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Our results suggest potential metabolomic mechanisms that could contribute to the earliest signs of cognitive decline. In particular, fatty acids may be associated with cognition in a manner that is more complex than previously suspected.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-200176","type":"journal-article","created":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T15:57:41Z","timestamp":1610121461000},"page":"1041-1054","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":14,"title":["Metabolites Associated with Early Cognitive Changes Implicated in Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"79","author":[{"given":"Burcu F.","family":"Darst","sequence":"first","affiliation":[{"name":"Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguang","family":"Huo","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin M.","family":"Jonaitis","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L.","family":"Koscik","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay R.","family":"Clark","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"},{"name":"Geriatric Research Education and Clinical Center, Wm. S. Middleton Memorial VA Hospital, Madison, WI, USA"},{"name":"Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiongshi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics & Medical Informatics, University of Wisconsin, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William S.","family":"Kremen","sequence":"additional","affiliation":[{"name":"University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol E.","family":"Franz","sequence":"additional","affiliation":[{"name":"University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brinda","family":"Rana","sequence":"additional","affiliation":[{"name":"University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Lyons","sequence":"additional","affiliation":[{"name":"Department of Psychological & Brain Sciences, Boston University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk J.","family":"Hogan","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"},{"name":"Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinying","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sterling C.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"},{"name":"Geriatric Research Education and Clinical Center, Wm. S. Middleton Memorial VA Hospital, Madison, WI, USA"},{"name":"Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne D.","family":"Engelman","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"},{"name":"Wisconsin Alzheimer\u2019s Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"},{"name":"Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24048"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.06.014"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2017.02.008"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00343"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70299-6"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006189"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.003"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2017.11.012"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2017.118"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2016.09.003"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3466"},{"key":"ref013","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201900177"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.1037\/0894-4105.9.3.313"},{"key":"ref015","doi-asserted-by":"publisher","DOI":"10.1016\/j.acn.2005.07.002"},{"key":"ref016","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.24.13547"},{"key":"ref017","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005291"},{"key":"ref018","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz378"},{"key":"ref019","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2015.12.009"},{"key":"ref020","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617711001524"},{"key":"ref021","doi-asserted-by":"publisher","DOI":"10.1177\/0891988705281882"},{"key":"ref022","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2017.11.007"},{"key":"ref023","first-page":"1","volume":"4","author":"Evans AM","year":"2014","journal-title":"Metabolomics"},{"key":"ref024","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-7-142"},{"key":"ref025","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.22211"},{"key":"ref026","author":"Rayner NW","year":"2016","journal-title":"The American Society of Human Genetics"},{"key":"ref027","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3656"},{"key":"ref028","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3643"},{"key":"ref029","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3679"},{"key":"ref030","volume-title":"Reitan Neuropsychological Test Battery: Therapy and clinical interpretation","author":"Reitan RM","year":"1985"},{"key":"ref031","author":"Trenerry MR","year":"1989","journal-title":"Stroop Neuropsychological Screening Test Manual"},{"key":"ref032","author":"Wechsler D","year":"1981","journal-title":"Wechsler Adult Intelligence Scale - Revised"},{"key":"ref033","author":"Schmidt M","year":"1996","journal-title":"Rey Auditory Verbal Learning Test: A Handbook"},{"key":"ref034","author":"Wechsler D","year":"1987","journal-title":"Wechsler Memory Scale-Revised"},{"key":"ref035","author":"Benedict RH","year":"1997","journal-title":"Brief Visuospatial Memory Test-Revised"},{"key":"ref036","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2018.11.006"},{"key":"ref037","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160195"},{"key":"ref038","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"ref039","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyg070"},{"key":"ref040","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3809"},{"key":"ref041","doi-asserted-by":"publisher","DOI":"10.1186\/s13742-015-0047-8"},{"key":"ref042","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"ref043","doi-asserted-by":"publisher","DOI":"10.1002\/cpbi.11"},{"key":"ref044","doi-asserted-by":"publisher","DOI":"10.1017\/thg.2012.86"},{"key":"ref045","first-page":"1","author":"Schoenborn CA","year":"2009","journal-title":"Natl Health Stat Report"},{"key":"ref046","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1811537116"},{"key":"ref047","doi-asserted-by":"publisher","DOI":"10.1037\/neu0000389"},{"key":"ref048","doi-asserted-by":"publisher","DOI":"10.1198\/073500102288618658"},{"key":"ref049","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-197503000-00005"},{"key":"ref050","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002266"},{"key":"ref051","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101837"},{"key":"ref052","doi-asserted-by":"publisher","DOI":"10.1172\/JCI89885"},{"key":"ref053","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M600029-JLR200"},{"key":"ref054","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2016.01.006"},{"key":"ref055","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2011.12.014"},{"key":"ref056","doi-asserted-by":"publisher","DOI":"10.3945\/an.113.004556"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-200176","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JAD-200176","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-200176","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:04:41Z","timestamp":1777370681000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-200176"}},"subtitle":[],"editor":[{"given":"Roger","family":"Dixon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,2,2]]},"references-count":56,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,2,2]]}},"alternative-id":["10.3233\/JAD-200176"],"URL":"https:\/\/doi.org\/10.3233\/jad-200176","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/436667","asserted-by":"object"}]},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,2]]}}}